This is the revised application for a project that examines the pathophysiologic basis for delusional thought in Alzheimer's disease (AD). Delusions are common in patients with AD and contribute substantially to behavioral disturbances and other morbid aspects of the illness. Despite increased recognition of the importance of noncognitive symptoms in AD, the neurobiology Of delusions is not well understood. The proposed project measures the relationship between delusions and regional brain function in patients both before and after a treatment intervention. Two hypotheses, supported by preliminary data, are tested: Among patients with AD, delusional thought is associated with reduced metabolic rate in specific subregions of the frontal cortex. This relationship is consistent across treatment conditions. With neuroleptic treatment for delusions in AD, clinical improvement in delusional thought is associated with frontal metabolic rate prior to treatment. Toe test these hypotheses, patients with AD (with and without delusions) undergo structured assessment to measure the severity of delusional thought and 18F-fluorodeoxyglucose positron emission tomography (PET) to measure metabolic rate in the whole frontal cortex, in subregions of the frontal cortex, and in other brain areas. Patients with delusions are then treated with haloperidol for 5 weeks. The structured clinical assessment and PET imaging are repeated after the treatment period. The relationship between delusions and cortical metabolism is examined in the pretreatment and posttreatment conditions, using sophisticated neuroimage analysis techniques. The cerebral metabolic correlates of clinical response (o treatment are also explored. The results of the study will improve understanding of the neurobiology of clinical symptoms and treatment response in AD. The project applies advanced research techniques to an important clinical problem. Dr. David Sultzer, the Principal investigator in the proposed project, is currently completing the 5-year NIMH Clinical Mental Health Academic Award in Geriatric Psychiatry. During the award period at UCLA, he has developed considerable skills in the assessment of noncognitive symptoms and PET imaging in AD that will